Irritable bowel syndrome (IBS) is a common functional gastrointestinal (Gl) disorder that affects 10-17% of women in industrialized nations. The costs of IBS are high, and in 2000 the direct and indirect costs of diagnosis and symptom management of IBS were estimated to be 1.66 billion dollars, making it not only costly to the individual, but also to the health care system. As a competitive renewal application this study proposes to build on our previously funded study in which symptom subtype and severity were related to both sleep characteristics (sleep efficiency, self report of poor sleep) and autonomic nervous system (ANS) balance. The current study is focused on exploring the role of acute stress exposure on night-time sleep, ANS balance, and neuroendocrine markers in women with severe IBS-diarrhea and IBS-constipation. This will be accomplished by describing and comparing women with severe diarrhea-predominant IBS (n=27), severe constipation-predominant IBS (n=27), and Controls (n=27) on measures of vagal tone and physiological arousal indicators under baseline conditions and in response to experimentally induced acture stress (anticipation of public speaking) conditions. Psychophysiological arousal measures include heart rate variability, psychological distress (diary measures, psychiatric history, history of abuse, coping style), and neuroendocrine markers (serial measures of night-time cortisol, ACTH, norepinephrine, epinephrine). Second, groups will be compared on indicators of objective (polysomnograpy) and subjective sleep measures using both self report data and 3 nights in the School of Nursing Sleep Laboratory. Third, this study will explore the relationships of serotonin reuptake transporter protein (SERT) polymorphisms (5- HTTLPR, STin2 VNTR, I425V) to self-reported and polysomnographic sleep, Gl symptoms, history of depression, childhood abuse, hassles severity and frequency, psychiatric distress, ANS and neuroendocrine in women with IBS as well as Controls. This study is important because health care providers working with IBS patients are challenged in that the underlying pathophysiology remains poorly defined and treatments are not universally effective. [unreadable] [unreadable] [unreadable] [unreadable]